Process for preparation of dihalogenoadamantanes

ABSTRACT

This invention discloses a process for preparing a dihalogenated adamantane by reacting an adamantane optionally substituted with alkyl at 1-position with a halosulfonic acid, comprising the first stage of monohalogenation conducted at −5 to 15° C. and then the second stage of dihalogenation conducted at 17 to 35° C., preferably in the absence of an organic solvent.

TECHNICAL FIELD

[0001] This invention relates to a process for preparing a dihalogenatedadamantane useful as a raw material for producing a functional orelectronic material.

BACKGROUND OF THE INVENTION

[0002] Adamantane derivatives have been expected to be used as a rawmaterial for producing a high-function material such as a highly heatresistance polymer material or an electronic material such as asemiconductor resist because they exhibit excellent heat resistance andtransparency. Among others, dihalogenated adamantanes are important asraw materials for preparing a variety of adamantane derivatives havingbifunctional groups.

[0003] A variety of halogenated adamantanes have been prepared fromadamantane, for example, by reacting adamantane with a haloalkane in thepresence of an aluminum halide [Synth. Commun., 19(9-10), 1697-1704(1989)] or by reacting adamantane with a haloalkane in the presence of acobalt salt [RU 2125551 (1999)]. These processes, however, generallyprovide a mixture of mono-, di-, and/or tri-halogenated adamantanes.Furthermore, such a mixture generally contains a monohalogenatedadamantane as a main product, with a lower yield of a dihalogenatedadamantane.

[0004] Tetrahedron Letters 31, 3191-3192 (1972) has disclosed a processfor selectively preparing a dihalogenated adamantane, where adamantaneis mixed and reacted with a halosulfonic acid at 20° C. In thissynthetic method, the reaction, however, sharply proceeds during theinitial stage. Thus, when using a sufficient amount of a halosulfonicacid in attempting to improve an yield, the reaction tends toexcessively proceed, leading to formation of trihalogenated derivatives.The above preparation process is, therefore, improper with respect to anyield of a dihalogenated adamantane. For example, when adamantane andchlorosulfonic acid are charged in the molar ratio of 1:8 and reactedfor about 10 hours, an yield of 1,3-dichloroadamantane is 80% or less asdetermined by gas chromatography.

[0005] For selectively preparing a dihalogenated adamantane, Zh. Org.Khim., 22 (3), 540-542 (1986) and Helv. Chim. Acta, 68 (5), 1196-1203(1985) have used an iron halide. However, when preparing a dihalogenatedadamantane using a metal compound, a dihalogenated adamantane preparedmay be frequently contaminated with a metal. In an electronic device,contamination with a trace amount of a metal may be deleterious to itsperformance. A dihalogenated adamantane prepared according the processcannot be, therefore, used for manufacturing such an electronic device.Further purification of a dihalogenated adamantane contaminated with ametal is cumbersome, leading to increase in a cost.

[0006] The above preparation process may provide a dihalogenatedadamantane in a relatively higher yield, but the dihalogenatedadamantane thus prepared inevitably contains several percents of amonohalogenated adamantane, which is an intermediate. For providing thehighly pure dihalogenated adamantane, separation of the monohalogenatedadamantane is essential. These compounds, however, exhibit very similarchemical properties, and thus cannot be separated by a common andconvenient method. They are, therefore, generally separated bychromatography. However, chromatographic separation can deal with asmall amount in a single run and takes much time, leading to loweroverall productivity. Thus, the procedure is not suitable for productionin a large scale.

SUMMARY OF THE INVENTION

[0007] We have intensely attempted to solve the above problems and havefinally found that these problems can be solved by reacting adamantaneand a halosulfonic acid under a particular temperature condition,achieving this invention.

[0008] An objective of this invention is, therefore, to provide aprocess for preparing a highly pure dihalogenated adamantane in a highyield under mild conditions without using a metal or metal salt.

[0009] This invention provides a process for preparing a dihalogenatedadamantane by reacting an adamantine which is optionally substitutedwith alkyl at 1-position with a halosulfonic acid, comprising the firststage of monohalogenation conducted at −5 to 15° C. and then the secondstage of dihalogenation conducted at 17 to 35° C.

DETAILED DESCRIPTION OF THE INVENTION

[0010] In this invention, the adamantane as a raw material is generallyunsubstituted, but may be optionally substituted with alkyl at1-position. The alkyl is preferably linear alkyl having 1 to 4 carbonatoms such as methyl, ethyl and propyl, particularly preferably methyl.

[0011] The halosulfonic acid used in this invention is a compoundrepresented by:

XSO₃H

[0012] wherein X represents halogen. Examples of halogen includesfluorine, chlorine, bromine and iodine. Specifically, the halosulfonicacid may be chlorosulfonic acid, bromosulfonic acid, iodosulfonic acidor the like. In the light of availability, chlorosulfonic acid isparticularly preferable.

[0013] In this invention, the adamantane optionally substituted withalkyl at 1-position (hereinafter, also referred to as “adamantanecompound”) is reacted with a halosulfonic acid to give a dihalogenatedadamantane.

[0014] When the adamantane compound is unsubstituted, a dihalogenatedadamantane as a main product is a 1,3-dihalogenated adamantanerepresented by formula (1):

[0015] Generally, in addition to the 1,3-dihalogenated adamantane, otherdihalogenated adamantanes may be formed in a small amount.

[0016] When the adamantane compound is substituted with alkyl at1-position, a dihalogenated adamantane as a main product is1-alkyl-3,5-dihalogenated adamantane represented by formula (2):

[0017] wherein R represents linear alkyl having 1 to 4 carbon atoms.

[0018] Generally, in addition to the 1-alkyl-3,5-dihalogenatedadamantane, other dihalogenated adamantanes may be formed in a smallamount.

[0019] In the synthetic reaction, there are no limitations to chargeratios for an adamantane compound and a halosulfonic acid. However,since an extremely small rate of the halosulfonic acid may lead toinadequate reaction, a molar ratio of the halosulfonic acid ispreferably two or more to the adamantane compound. As described later, amolar ratio of the halosulfonic acid to the adamantane compound is 5 to15, most preferably 8 to 12 for allowing the halosulfonic acid tosufficiently function as a reaction solvent and improving an yield whenconducting the reaction without using an organic solvent.

[0020] There are no limitations to a procedure for mixing the adamantanecompound and the halosulfonic acid. Preferably, the halosulfonic acid isadded dropwise to the adamantane or a solution of the adamantane in anorganic solvent.

[0021] This invention is primarily characterized in that in the reactionbetween the above adamantane compound and a halosulfonic acid, the firstmonohalogenation is conducted at −5 to 15° C. and then the seconddihalogenation is conducted at 17 to 35° C. Such a characteristictwo-stage reaction at different temperatures can reduce the amount ofbyproducts such as trihalogenated adamantanes to give more selectively adesired dihalogenated adamantane.

[0022] Generally in the reaction between an adamantane compound and ahalosulfonic acid, the adamantane compound is first monohalogenated(hereinafter, the reaction is also referred to as a “monohalogenation”).Then, halogenation proceeds to form a dihalogenated derivative(hereinafter, the reaction is also referred to as a “dihalogenation”).Further halogenation may proceed to give tri- and tetra-halogenatedderivatives in sequence. When the reaction is conducted maintaining areaction temperature in the range of −5 to 15° C., monohalogenationproceeds, while under the temperature condition, a further halogenationof a monohalogenated derivative to a dihalogenated derivative littleproceeds. Dihalogenation rapidly proceeds at a reaction temperature ofmore than 17° C.

[0023] If the reaction temperature is 17° C. or higher from the initialstage of the reaction, the reaction rapidly proceeds from the initialstage to give a dihalogenated derivative and finally halogenation tendsto rush to provide trihalogenated derivatives. Thus, under thetemperature condition, trihalogenated derivatives are formed in asignificant amount, resulting in a lower yield of the dihalogenatedadamantane.

[0024] In contrast, when a reaction temperature is set in two steps suchthat the reaction proceeds under mild conditions in the initial stage, areaction further forming a trihalogenated derivative after forming ofthe dihalogenated derivative little proceeds even when a temperature isset to 17° C. or higher in the subsequent second stage. As a result, thedihalogenated adamantane can be formed in a higher yield.

[0025] If a reaction temperature is lower than 5° C., monohalogenationdoes not sufficiently proceed. Thus, a reaction temperature in the firststage is preferably 5 to 15° C. If a reaction temperature is lower than−5° C., monohalogenation little proceeds.

[0026] During the step of mixing an adamantane compound with ahalosulfonic acid, a liquid temperature is preferably maintained at 5°C. or lower to avoid a runaway reaction.

[0027] The monohalogenation in the first stage is continued until thecharged adamantane compound is substantially monohalogenated. A reactiontime is generally at least 30 min, preferably 1 to 3 hours.

[0028] After the first monohalogenation stage, the second stagedihalogenation is conducted. A reaction temperature in the second stageis suitably 17 to 25° C. in the light of providing a dihalogenatedadamantane in a particularly higher yield. If the reaction temperaturein the second stage is higher than 35° C., trihalogenation of thedihalogenated adamantane tends to considerably proceed.

[0029] It is necessary to continue the second reaction untildihalogenation adequately proceeds. However, an excessively longerreaction time may lead to gradual formation of trihalogenatedadamantanes. Thus, a reaction time is preferably 1 to 24 hours,particularly 3 to 8 hours.

[0030] If desired, a reaction temperature may be varied in multiplesteps within the temperature range defined above in each of the firstand the second stages. A reaction pressure in each reaction stage isgenerally, but not limited to, an ambient pressure.

[0031] The above two-stage reaction may be conducted in the absence orpresence of an organic solvent. However, the reaction is particularlypreferably conducted in the absence of an organic solvent, where ahalosulfonic acid may be also used as a solvent.

[0032] An adamantane compound or dihalogenated adamantane is littlesoluble in a halosulfonic acid whereas a monohalogenated adamantane issignificantly soluble in a halosulfonic acid. A halosulfonic acidexhibits such a specific dissolution property. Therefore, without anorganic solvent, a halosulfonic acid as a reaction reagent may be alsoused as a reaction solvent to efficiently utilize the above specificdissolution property of the halosulfonic acid. Thus, as described below,a dihalogenated adamantane can be selectively provided in a higherpurity.

[0033] Specifically, on charging an adamantane compound and ahalosulfonic acid, a reaction mixture is initially a suspension in whichthe adamantane compound is suspended. As the first stage reactionproceeds over time to produce a monohalogenated adamantane, the reactionis changed into a clear homogeneous solution because the product issoluble in the halosulfonic acid. Then, the monohalogenated adamantanethus formed is smoothly subjected to further halogenation in thehalosulfonic acid to give a dihalogenated derivative. The dihalogenatedadamantane thus formed is, however, substantially insoluble in thehalosulfonic acid as described above, so that most of the productprecipitates. As a result, the reaction mixture again becomes asuspension. When the dihalogenated adamantane have thus precipitated inthe halosulfonic acid, the dihalogenated adamantane becomessignificantly unreactive to the halosulfonic acid. Consequently,formation of trihalogenated adamantanes as byproducts can besubstantially reduced in the second stage reaction.

[0034] In the first stage reaction, as monohalogenation proceeds, areaction mixture changes from a suspension to a homogeneous solution.Such change allows the endpoint of the first stage reaction to bevisually determined with ease. Thus, it can eliminate the problems thatwhile the first stage reaction has not adequately proceeded, the secondstage reaction is initiated, leading to increase in an amount oftrihalogenated adamantanes formed and that the first stage reaction iscontinued for an unnecessarily longer time.

[0035] Precipitation of the dihalogenated adamantane formed during thesecond stage reaction is very advantageous to isolation of the desiredproduct. Specifically, when producing a crude dihalogenated adamantaneby reacting an adamantane compound with a halosulfonic acid as usual,separation of the desired dihalogenated adamantane from amonohalogenated adamantane having physico-chemical properties similar tothose of the dihalogenated adamantane is generally conducted by acumbersome purification procedure such as chromatography.

[0036] In contrast, when the reaction is conducted in the absence of anorganic solvent to produce a desired dihalogenated adamantane suspendedin the reaction as is in this invention, trihalogenated adamantanes arelittle formed as described above. Furthermore, the unreactedmonohalogenated adamantane is dissolved in the reaction mixture.Therefore, the reaction mixture can be filtered to easily isolate thehighly pure dihalogenated adamantane.

[0037] The filtration is preferably conducted under nitrogen atmosphere.If a temperature of the reaction during filtration is higher than theupper limit of the temperature range in the second stage reaction, theconversion of the dihalogenated adamantane into a trihalogenatedadamantane may proceed, and a solubility of the dihalogenated adamantanemay be increased, leading to reduction in an yield. It is, therefore,preferable to filtrate the reaction mixture within the temperature rangeof the second stage reaction.

[0038] The precipitate of the dihalogenated adamantane thus obtained maybe further purified by an appropriate method such as washing with water,extracted with a solvent and crystallization.

[0039] When the reaction is conducted in an organic solvent, the organicsolvent may be any of those which are unreactive to the halosulfonicacid; for example, chlorinated solvents such as dichloromethane and1,2-dichloroethane.

[0040] The amount of the organic solvent is not limited as long as itcan adequately dissolve reactants and does not significantly reduce abatch yield. Specifically, the amount is preferably 5 to 20 parts byweight to one part of the adamantane compound.

[0041] In this reaction using an organic solvent, a dihalogenatedadamantane produced is generally dissolved in a reaction mixture at theend of the second stage reaction. The dihalogenated adamantane can beisolated from the reaction mixture, for example, by adding ice-water tothe reaction mixture to decompose the halosulfonic acid, separating theorganic solvent layer containing the dihalogenated adamantane from theaqueous layer, washing the organic layer, evaporating the organic layerto give a residue, which is then dried and crystallized.

[0042] An equipment used in the reaction according to this inventionpreferably has a structure in which contact of the reaction system withthe air can be avoided. Such a structure can prevent generation of anacid gas due to decomposition of the halosulfonic acid by its reactionwith moisture. Before conducting the reaction, the atmosphere inside ofthe equipment is sufficiently replaced with an inert gas such asnitrogen and dried. It is preferable to close the system or continuouslyfeed an inert gas such as nitrogen into the system during the reaction.

[0043] The process of this invention is based on a two-stage reactionunder controlling certain temperature, so that a dihalogenatedadamantane can be prepared in a higher yield under mild conditions,without using a metal or metal salt which may contaminate the product tocause various problems. Furthermore, when the reaction is conducted inthe absence of a solvent, difference in a solubility between adihalogenated adamantane and a monohalogenated adamantane in ahalosulfonic acid can be utilized to easily isolate and purify thedihalogenated adamantane with a higher yield.

[0044] A dihalogenated adamantane prepared by the process of thisinvention may be, for example, hydrolyzed or ammonolyzed into anadamantane diol or diaminoadamantane, respectively, which can bebeneficially used as a raw material for a functional material such as aheat resistant polymer or an electronic material such as a resist.

EXAMPLES

[0045] This invention will be more specifically described with referenceto, but not limited to, Examples.

Example 1

[0046] In a 100 mL three-necked flask was placed 5.0 g of adamantane(0.037 mol) and then the inside of the flask was dried by purging withnitrogen gas. Under the nitrogen stream, the flask was cooled to aninternal temperature of 0° C., and then 43.1 g of chlorosulfonic acid(0.37 mol) was added dropwise. The reaction mixture as a suspension waswarmed to 10° C. to initiate the first stage reaction witheffervescence. The reaction was maintained at the temperature untileffervescence ceased. After 2 hours, the reaction became a clear andhomogeneous solution.

[0047] The reaction mixture was warmed to 20° C. to initiate the secondstage reaction with mild effervescence again. The reaction wasmaintained under the conditions for 5 hours. The reaction mixture as asuspension was filtrated under a nitrogen atmosphere. The solid thusobtained was poured into ice-water and extracted with chloroform. Afterreplacing the solvent with hexane, the organic layer was filtrated.After adding charcoal, the filtrate was again filtrated. Afterevaporation, the residue was dried to give 7.0 g of a white solid(yield: 93%).

[0048] The while solid contained 1,3-dichloroadamantane in a purity of94% as determined by gas chromatography.

Comparative Example 1

[0049] Halogenation was conducted as described in Example 1, except thatchlorosulfonic acid was added to 5.0 g of adamantane (0.037 mol) at 20°C. and the reaction was continued at the temperature for 7 hours, togive 5.6 g of a white solid (yield: 75%).

[0050] The analysis results indicated that the white solid contained1,3-dichloroadamantane in a purity of 78%.

Comparative Example 2

[0051] As described in Example 1, chlorosulfonic acid was added dropwiseto 5.0 g of adamantane (0.037 mol) at 10° C. and the reaction wascontinued for 2 hours. The reaction mixture became a clear andhomogeneous solution. Then, the reaction mixture was warmed to 40° C.and the reaction was continued for 5 hours. The reaction was thenprocessed as described in Example 1 to give 5.3 g of a white solid(yield: 71%). The analysis results indicated that the white solidcontained 1,3-dichloroadamantane in a purity of 80%.

Example 2

[0052] Halogenation was conducted as described in Example 1, except thata reaction temperature during the first stage was 15° C. and one hourwas taken for making the reaction mixture clear and homogeneous, to give6.7 g of a white solid (yield: 89%).

[0053] The analysis results indicated that the white solid contained1,3-dichloroadamantane in a purity of 91%.

Example 3

[0054] Halogenation was conducted as described in Example 1, except thatin the second stage, a reaction temperature was 30° C. and the reactiontime was 3 hours, to give 6.8 g of a white solid (yield: 90%).

[0055] The analysis results indicated that the white solid contained1,3-dichloroadamantane in a purity of 89%.

Example 4

[0056] Halogenation was conducted as described in Example 1, except thatthe amount of chlorosulfonic acid was 25.9 g (0.22 mol) and a reactiontime of the second stage was 8 hours, to give 6.5 g of a white solid(yield: 86%).

[0057] The analysis results indicated that the white solid contained1,3-dichloroadamantane in a purity of 92%.

Example 5

[0058] Halogenation was conducted as described in Example 1, exceptsubstituting 5.5 g of 1-methyladamantane (0.037 mol) for 5.0 g ofadamantane (0.037 mol), to give 7.2 g of a white solid (yield: 90%).

[0059] The analysis results indicated that the white solid contained1-methyl-3,5-dichloroadamantane in a purity of 90%.

Example 6

[0060] Halogenation was conducted as described in Example 1, exceptsubstituting 59.6 g of bromosulfonic acid (0.37 mol) for 43 g ofchlorosulfonic acid (0.37 mol), to give 9.5 g of a white solid (yield:88%).

[0061] The analysis results indicated that the white solid contained1,3-dibromoadamantane in a purity of 92%.

Example 7

[0062] In a 100 mL three-necked flask was placed 5.0 g of adamantane(0.037 mol) and then the inside of the flask was dried by purging withnitrogen gas. Under the nitrogen stream, 50 mL of dehydrateddichloromethane was added and the mixture was cooled to 0° C. To themixture was then added dropwise 43.1 g of chlorosulfonic acid (0.37mol). The reaction as a suspension was warmed to 10° C. to initiate thefirst stage reaction with effervescence, and the reaction was continuedat 10° C. for 2 hours.

[0063] The reaction mixture was warmed to 20° C. to initiate the secondstage reaction with mild effervescence again, and the reaction wascontinued for 5 hours. The reaction solution was poured into ice-water,and the mixture was stirred until the mixture was warmed to roomtemperature. The mixture was extracted with 100 mL of dichloromethanetwice. The combined extracts were washed with water and evaporated. Theresidue was dissolved in hexane and the solution was filtrated. Afteradding charcoal, the solution was again filtrated and the solvent wasevaporated. The residue was dried to give 6.8 g of a white solid (yield:90%).

[0064] The white solid contained 1,3-dichloroadamantane in a purity of89% as determined by gas chromatography.

Comparative Example 3

[0065] In a 100 mL three-necked flask was placed 5.0 g of adamantane(0.037 mol) and then the inside of the flask was dried by purging withnitrogen gas. Under the nitrogen stream, into the three-necked flaskwere added 50 mL of 2-chloro-2-methylpropane and 1.0 g of aluminumchloride, and then the mixture was refluxed for 8 hours. The reactionsolution was poured into ice-water, and the mixture was stirred until itwas warmed to room temperature. The solution was filtrated and extractedwith chloroform twice. The combined extracts were washed with water onceand evaporated. The residue was dissolved in hexane and the solution wasfiltrated. After adding charcoal, the solution was again filtrated. Thesolvent was evaporated and the residue was dried to give 5.3 g of awhite solid.

[0066] The white solid contained 90% of 1-chloroadamantane and 5% of1,3-dichloroadamantane as determined by gas chromatography.

1. A process for preparing a dihalogenated adamantane by reacting anadamantane optionally substituted with alkyl at 1-position with ahalosulfonic acid, comprising the first stage of monohalogenationconducted at −5 to 15° C. and then the second stage of dihalogenationconducted at 17 to 35° C.
 2. The process for preparing a dihalogenatedadamantane as claimed in claim 1 wherein the first stage ofmonohalogenation and the second stage of dihalogenation are conducted inthe absence of an organic solvent.
 3. The process for preparing adihalogenated adamantane as claimed in claim 2 wherein the first stageof monohalogenation is continued until a reaction mixture becomes ahomogenous solution.
 4. The process for preparing a dihalogenatedadamantane as claimed in claim 2 wherein the reaction mixture after thesecond stage of dihalogenation is filtrated to isolate the dihalogenatedadamantane.
 5. The process for preparing a dihalogenated adamantane asclaimed in claim 1 wherein the halosulfonic acid is charged in a molarratio of 5 to 15 to the adamantane optionally substituted with alkyl at1-position.